Characterization of the retinoid orphan-related receptor-alpha coactivator binding interface: A structural basis for ligand-independent transcription

The retinoid orphan-related receptor-alpha (RORalpha) is a member of the ROR subfamily of orphan receptors and acts as a constitutive activator of transcription in the absence of exogenous ligands. To understand the basis of this activity, we constructed a homology model of Rill using the closely related TRbeta as a template. Molecular modeling suggested that bulky hydrophobic side chains occupy the RORa ligand cavity leaving a small but distinct cavity that may be involved in receptor stabilization. This model was subject to docking simulation with a receptor-interacting peptide from the steroid receptor coactivator, GR-interacting protein-1, which delineated a coactivator binding surface consisting of the signature motif spanning helices 3-5 and helix 12 [activation function 2 (AF2)]. Probing this surface with scanning alanine mutagenesis showed structural and functional equivalence between homologous residues of RORalpha and TRbeta. This was surprising (given that Rill is a ligand-independent activator, whereas TRbeta has an absolute requirement for ligand) and prompted us to use molecular modeling to identify differences between Rill and TRbeta in the way that the All helix interacts with the rest of the receptor. Modeling highlighted a nonconserved amino acid in helix 11 of RORa (Phe491) and a short-length of 3.10 helix at the N terminus of AF2 which we suggest i) ensures that AF2 is locked permanently in the holoconformation described for other liganded receptors and thus 2) enables ligand-independent recruitment of coactivators. Consistent with this, mutation of RORa Phe491 to either methionine or alanine (methionine is the homologous residue in TRbeta), reduced and ablated transcriptional activation and recruitment of coactivators, respectively. Furthermore, we were able to reconstitute transcriptional activity for both a deletion mutant of Ill lacking All and Phe491 Met, by overexpression of a GAL-AF2 fusion protein, demonstrating ligand-independent recruitment of AF2 and a role for Phe491 in recruiting AF2.

Estudo do efeito da adição de gás condensado sobre o ponto de fluidez e a viscosidade de petróleos pesados

Neste trabalho foi estudado o comportamento de quatro óleos pesados, com densidade API variando de 13,7 a 21,6, frente à adição de gás condensado, com o objetivo de se obter informações relevantes para o processo de escoamento destes óleos. Assim, foi analisado o comportamento da densidade à 20 °C, pontos de fluidez máximo e mínimo, e viscosidade dinâmica à 50 °C dos óleos contendo diferentes concentrações de gás condensado. Também foi analisado o efeito da variação da temperatura sobre a viscosidade dos óleos crus, e, adicionalmente, após o estudo do efeito do gás condensado sobre os óleos, foi avaliado o comportamento da viscosidade dinâmica dos mesmos com a adição de diferentes solventes orgânicos (querosene, aguarrás e tolueno). Os resultados obtidos indicaram que o gás condensado foi eficiente para a redução da densidade, dos pontos de fluidez máximo e mínimo e da viscosidade dos quatros óleos analisados. O óleo A apresentou uma taxa de decaimento da densidade mais baixa do que os outros óleos e foi o que apresentou o comportamento mais próximo de mistura ideal. A amostra de óleo mais pesada (óleo D) foi a que apresentou as maiores variações nos valores dos pontos de fluidez máximo e mínimo com a adição de condensado, chegando a reduzir um total de 19 °C no ponto de fluidez máximo e um total de 21 °C no ponto de fluidez mínimo com a adição de apenas 10,7% v/v de gás condensado. Nos resultados obtidos nas análises da viscosidade dinâmica observou-se que a grande maioria das misturas preparadas apresentou um comportamento de fluido newtoniano. Todas as amostras apresentaram uma notável diminuição da sua viscosidade, chegando a atingir valores percentuais de redução de viscosidade que variaram entre 75 e 91%, na concentração de 14% v/v de gás condensado. A partir desta concentração a viscosidade continua a decair, porém de forma mais atenuada, e o uso do condensado acima desta concentração pode significar gastos desnecessários com o solvente com a finalidade de se reduzir a viscosidade de óleos pesados. O óleo D foi o que apresentou os maiores percentuais de redução da viscosidade enquanto o óleo B foi o que apresentou os mais baixos valores. Comparando o gás condensado aos outros três solventes orgânicos testados, o condensado apresentou um comportamento bem semelhante ao tolueno quando analisadas as suas capacidades de redução da viscosidade dos óleos estudados.

Análise de conforto de ciclistas por simulação multicorpo

Este trabalho apresenta um estudo sobre o comportamento dinâmico das bicicletas com o principal objectivo de quantificar o conforto de um ciclista. Neste trabalho serão estudados dois tipos de bicicletas: uma apenas com suspensão dianteira e outra com suspensão dianteira e traseira (ou suspensão total), e três classes de pavimento: um mais sinuoso, um mais suave e um intermédio. Para cada uma destas situações o que se pretende é analisar a quantidade de vibração que é transmitida para o corpo do ciclista através dos três pontos de contacto existentes entre ambos: Assento, guiador e pedais. Os valores obtidos são comparados entre os vários casos e também com valores referência, fornecidos por normas, afim de analisar a situação de conforto do ciclista. Após a realização dos estudos o que se verificou é que o ciclista está numa situação mais desconfortável em pisos mais sinuosos, e que nesta situação se utilizar uma bicicleta de suspensão total está sujeito a vibrações inferiores. No entanto, o mais importante a concluir é que em qualquer uma das situações estudadas o ciclista encontra-se sempre dentro de uma zona conforto segundo as normas utilizadas.

Análise de risco em organizações: caso de estudo

Dissertação Final de Mestrado para obtenção do grau de Mestre em Engenharia Mecânica no perfil de Manutenção e Produção

The use of non-standard CT conversion ramps for Monte Carlo verification of 6 MV prostate IMRT plans

Monte Carlo (MC) dose calculation algorithms have been widely used to verify the accuracy of intensity-modulated radiotherapy (IMRT) dose distributions computed by conventional algorithms due to the ability to precisely account for the effects of tissue inhomogeneities and multileaf collimator characteristics. Both algorithms present, however, a particular difference in terms of dose calculation and report. Whereas dose from conventional methods is traditionally computed and reported as the water-equivalent dose (Dw), MC dose algorithms calculate and report dose to medium (Dm). In order to compare consistently both methods, the conversion of MC Dm into Dw is therefore necessary. This study aims to assess the effect of applying the conversion of MC-based Dm distributions to Dw for prostate IMRT plans generated for 6 MV photon beams. MC phantoms were created from the patient CT images using three different ramps to convert CT numbers into material and mass density: a conventional four material ramp (CTCREATE) and two simplified CT conversion ramps: (1) air and water with variable densities and (2) air and water with unit density. MC simulations were performed using the BEAMnrc code for the treatment head simulation and the DOSXYZnrc code for the patient dose calculation. The conversion of Dm to Dw by scaling with the stopping power ratios of water to medium was also performed in a post-MC calculation process. The comparison of MC dose distributions calculated in conventional and simplified (water with variable densities) phantoms showed that the effect of material composition on dose-volume histograms (DVH) was less than 1% for soft tissue and about 2.5% near and inside bone structures. The effect of material density on DVH was less than 1% for all tissues through the comparison of MC distributions performed in the two simplified phantoms considering water. Additionally, MC dose distributions were compared with the predictions from an Eclipse treatment planning system (TPS), which employed a pencil beam convolution (PBC) algorithm with Modified Batho Power Law heterogeneity correction. Eclipse PBC and MC calculations (conventional and simplified phantoms) agreed well (<1%) for soft tissues. For femoral heads, differences up to 3% were observed between the DVH for Eclipse PBC and MC calculated in conventional phantoms. The use of the CT conversion ramp of water with variable densities for MC simulations showed no dose discrepancies (0.5%) with the PBC algorithm. Moreover, converting Dm to Dw using mass stopping power ratios resulted in a significant shift (up to 6%) in the DVH for the femoral heads compared to the Eclipse PBC one. Our results show that, for prostate IMRT plans delivered with 6 MV photon beams, no conversion of MC dose from medium to water using stopping power ratio is needed. In contrast, MC dose calculations using water with variable density may be a simple way to solve the problem found using the dose conversion method based on the stopping power ratio.

Embedded platform for ECG biometric recognition

Trabalho Final de Mestrado para obtenção do grau de Mestre em Engenharia de Electrónica e Telecomunicações

Impacto da influência do ar novo na climatização de edifícios

Este trabalho surgiu do âmbito da Tese de Dissertação do Mestrado em Energias Sustentáveis do Instituto Superior de Engenharia do Porto, tendo o acompanhamento dos orientadores da empresa Laboratório Ecotermolab do Instituto de Soldadura e Qualidade e do Instituto Superior de Engenharia do Porto, de forma a garantir a linha traçada indo de acordo aos objectivos propostos. A presente tese abordou o estudo do impacto da influência do ar novo na climatização de edifícios, tendo como base de apoio à análise a simulação dinâmica do edifício em condições reais num programa adequado, acreditado pela norma ASHRAE 140-2004. Este trabalho pretendeu evidenciar qual o impacto da influência do ar novo na climatização de um edifício com a conjugação de vários factores, tais como, ocupação, actividades e padrões de utilização (horários), iluminação e equipamentos, estudando ainda a possibilidade do sistema funcionar em regime de “Free-Cooling”. O princípio partiu fundamentalmente por determinar até que ponto se pode climatizar recorrendo único e exclusivamente à introdução de ar novo em regime de “Free-Cooling”, através de um sistema tudo-ar de Volume de Ar Variável - VAV, sem o apoio de qualquer outro sistema de climatização auxiliar localizado no espaço, respeitando os caudais mínimos impostos pelo RSECE (Decreto-Lei 79/2006). Numa primeira fase foram identificados todos os dados relativos à determinação das cargas térmicas do edifício, tendo em conta todos os factores e contributos alusivos ao valor da carga térmica, tais como a transmissão de calor e seus constituintes, a iluminação, a ventilação, o uso de equipamentos e os níveis de ocupação. Consequentemente foram elaboradas diversas simulações dinâmicas com o recurso ao programa EnergyPlus integrado no DesignBuilder, conjugando variáveis desde as envolventes à própria arquitectura, perfis de utilização ocupacional, equipamentos e taxas de renovação de ar nos diferentes espaços do edifício em estudo. Obtiveram-se vários modelos de forma a promover um estudo comparativo e aprofundado que permitisse determinar o impacto do ar novo na climatização do edifício, perspectivando a capacidade funcional do sistema funcionar em regime de “Free-Cooling”. Deste modo, a análise e comparação dos dados obtidos permitiram chegar às seguintes conclusões: Tendo em consideração que para necessidades de arrefecimento bastante elevadas, o “Free-Cooling” diurno revelou-se pouco eficaz ou quase nulo, para o tipo de clima verificado em Portugal, pois o diferencial de temperatura existente entre o exterior e o interior não é suficiente de modo a tornar possível a remoção das cargas de forma a baixar a temperatura interior para o intervalo de conforto. Em relação ao “Free-Cooling” em horário nocturno ou pós-laboral, este revelou-se bem mais eficiente. Obtiveram-se prestações muito interessantes sobretudo durante as estações de aquecimento e meia-estação, tendo em consideração o facto de existir necessidades de arrefecimento mesmo durante a estação de aquecimento. Referente à ventilação nocturna, isto é, em períodos de madrugada e fecho do edifício, concluiu-se que tal contribui para um abaixamento do calor acumulado durante o dia nos materiais construtivos do edifício e que é libertado ou restituído posteriormente para os espaços em períodos mais tardios. De entre as seguintes variáveis, aumento de caudal de ar novo insuflado e o diferencial de temperatura existente entre o ar exterior e interior, ficou demonstrado que este último teria maior peso contributivo na remoção do calor. Por fim, é ponto assente que de um modo geral, um sistema de climatização será sempre indispensável devido a cargas internas elevadas, requisitos interiores de temperatura e humidade, sendo no entanto aconselhado o “Free- Cooling” como um opção viável a incorporar na solução de climatização, de forma a promover o arrefecimento natural, a redução do consumo energético e a introdução activa de ar novo.

Adaptive learning in agents behaviour: a framework for electricity markets simulation

Electricity markets are complex environments with very particular characteristics. A critical issue regarding these specific characteristics concerns the constant changes they are subject to. This is a result of the electricity markets’ restructuring, which was performed so that the competitiveness could be increased, but it also had exponential implications in the increase of the complexity and unpredictability in those markets scope. The constant growth in markets unpredictability resulted in an amplified need for market intervenient entities in foreseeing market behaviour. The need for understanding the market mechanisms and how the involved players’ interaction affects the outcomes of the markets, contributed to the growth of usage of simulation tools. Multi-agent based software is particularly well fitted to analyze dynamic and adaptive systems with complex interactions among its constituents, such as electricity markets. This dissertation presents ALBidS – Adaptive Learning strategic Bidding System, a multiagent system created to provide decision support to market negotiating players. This system is integrated with the MASCEM electricity market simulator, so that its advantage in supporting a market player can be tested using cases based on real markets’ data. ALBidS considers several different methodologies based on very distinct approaches, to provide alternative suggestions of which are the best actions for the supported player to perform. The approach chosen as the players’ actual action is selected by the employment of reinforcement learning algorithms, which for each different situation, simulation circumstances and context, decides which proposed action is the one with higher possibility of achieving the most success. Some of the considered approaches are supported by a mechanism that creates profiles of competitor players. These profiles are built accordingly to their observed past actions and reactions when faced with specific situations, such as success and failure. The system’s context awareness and simulation circumstances analysis, both in terms of results performance and execution time adaptation, are complementary mechanisms, which endow ALBidS with further adaptation and learning capabilities.

Notional processors: an approach for multiprocessor scheduling

Consider the problem of designing an algorithm with a high utilisation bound for scheduling sporadic tasks with implicit deadlines on identical processors. A task is characterised by its minimum interarrival time and its execution time. Task preemption and migration is permitted. Still, low preemption and migration counts are desirable. We formulate an algorithm with a utilisation bound no less than 66.¯6%, characterised by worst-case preemption counts comparing favorably against the state-of-the-art.

A two-competitive approximate schedulability analysis of CAN

Consider the problem of deciding whether a set of n sporadic message streams meet deadlines on a Controller Area Network (CAN) bus for a specified priority assignment. It is assumed that message streams have implicit deadlines and no release jitter. An algorithm to solve this problem is well known but unfortunately it time complexity is non-polynomial. We present an algorithm with polynomial time-complexity for computing an upper bound on the response times. Clearly, if the upper bound on the response time does not exceed the deadline then all deadlines are met. The pessimism of our approach is proven: if the upper bound of the response time exceeds the deadline then the response time exceeds the deadline as well for a CAN network with half the speed.

Autonomous behaviors for an unmanned mini-aerial vehicle

This thesis aims at addressing the development of autonomous behaviors, for search and exploration with a mini-UAV (Unmanned Aerial Vehicle), or also called MAV (Mini Aerial Vehicle) prototype, in order to gather information in rescue scenarios. The platform used in this work is a four rotor helicopter, known as quad-rotor from the German company Ascending Technologies GmbH, which is later assembled with a on-board processing unit (i.e. a tiny light weight computer) and a on-board sensor suite (i.e. 2D-LIDAR and Ultrasonic Sonar). This work can be divided into two phases. In the first phase an Indoor Position Tracking system was settled in order to obtain the Cartesian coordinates (i.e. X, Y, Z) and orientation (i.e.heading) which provides the relative position and orientation of the platform. The second phase was the design and implementation of medium/high level controllers on each command input in order to autonomously control the aircraft position, which is the first step towards an autonomous hovering flight, and any autonomous behavior (e.g. Landing, Object avoidance, Follow the wall). The main work is carried out in the Laboratory ”Intelligent Systems for Emergencies and Civil Defense”, in collaboration with ”Dipartimento di Informatica e Sistemistica” of Sapienza Univ. of Rome and ”Istituto Superiore Antincendi” of the Italian Firemen Department.

H.264/AVC backward compatible Bit-Depth scalable video coding

As high dynamic range video is gaining popularity, video coding solutions able to efficiently provide both low and high dynamic range video, notably with a single bitstream, are increasingly important. While simulcasting can provide both dynamic range videos at the cost of some compression efficiency penalty, bit-depth scalable video coding can provide a better trade-off between compression efficiency, adaptation flexibility and computational complexity. Considering the widespread use of H.264/AVC video, this paper proposes a H.264/AVC backward compatible bit-depth scalable video coding solution offering a low dynamic range base layer and two high dynamic range enhancement layers with different qualities, at low complexity. Experimental results show that the proposed solution has an acceptable rate-distortion performance penalty regarding the HDR H.264/AVC single-layer coding solution.

Mobile collaborative cloudless computing

Although the computational power of mobile devices has been increasing, it is still not enough for some classes of applications. In the present, these applications delegate the computing power burden on servers located on the Internet. This model assumes an always-on Internet connectivity and implies a non-negligible latency. The thesis addresses the challenges and contributions posed to the application of a mobile collaborative computing environment concept to wireless networks. The goal is to define a reference architecture for high performance mobile applications. Current work is focused on efficient data dissemination on a highly transitive environment, suitable to many mobile applications and also to the reputation and incentive system available on this mobile collaborative computing environment. For this we are improving our already published reputation/incentive algorithm with knowledge from the usage pattern from the eduroam wireless network in the Lisbon area.

Model for the evaluation of drug-dispensing services in primary health care

OBJECTIVE To develop a model for evaluating the efficacy of drug-dispensing service in primary health care. METHODS An efficacy criterion was adopted to determine the level of achievement of the service objectives. The evaluation model was developed on the basis of a literature search and discussions with experts. The applicability test of the model was conducted in 15 primary health care units in the city of Florianópolis, state of Santa Catarina, in 2010, and data were recorded in structured and pretested questionnaires. RESULTS The model developed was evaluated using five dimensions of analysis for analysis. The model was suitable for evaluating service efficacy and helped to identify the critical points of each service dimension. CONCLUSIONS Adaptations to the data collection technique may be required to adjust for the reality and needs of each situation. The evaluation of the drug-dispensing service should promote adequate access to medications supplied through the public health system.

Assessment of climate change statistical downscaling methods: Application and comparison of two statistical methods to a single site in Lisbon

Dissertação apresentada na Faculdade de Ciências e Tecnologia da Universidade Nova de Lisboa para a obtenção do grau de Mestre em Engenharia do Ambiente